BECC Adjuvanted Vaccine Provides Protection from Homologous and Heterologous Infuenza A Infections

Abstract

Influenza A virus (IAV) is a leading cause of mild to severe respiratory disease worldwide with significant infections resulting in hospitalization or death, especially in older people, young children and people with comorbidities. Influenza virus is characterized for its high rate of mutation causing an antigen drift in its glycoprotein that allows the virus to evade the host immune system with new emerging variants. Vaccine production changes annually in order to match circulating strains but predicting these new variants can become challenging. MF59, a squalene oil emulsion, is currently the only approved Influenza vaccine. Adjuvant is used to cause an enhanced immune response with the vaccination, however is still limited to people aged 65 years and older. Using formulations of oil emulsion or aluminum hydroxide (alum) creates adjuvants that allows for an activation of a Th2 response. Alternatively, the adjuvant monophosphoryl lipid A, activates aTh1 response leading to a proinflammatory response. New technology has led to a novel creation of adjuvants by the use of Bacterial Enzymatic Combinatorial Chemistry (BECC) system that produces TLR4 immunostimulatory molecules. These molecules drive a balanced Th1/Th2 response and enhanced immunogenicity in combination with a HA IAV vaccine. These BECC/HA vaccines display superior protection compared to standard adjuvants when challenged with a homologous IAV strain (NL/09), heterologous IAV strain (Sing/15) in a BALB/c mouse model. Formulating with HA/BECC requires less antigen, and works with only a single vaccination. The BECC adjuvant may allow for improved efficacy and broader protection utilizing current Influenza vaccines and potentially other in the future.